Stroke remains the leading cause of long-term disability in the US. Neural plasticity is thought to be one of the major mechanisms underlying functional recovery after central nervous system CNS injury. Because neuronal networks are highly plastic and reorganize with activity, changes at the neuronal network level are very likely to underlie major and fundamental aspects of ischemia-related functional deficits and recovery. Constraint-induced movement therapy (CIMT), the forced use of the affected limb by immobilization of the healthy limb, has shown promise in enhancing motor function recovery in some chronic stroke patients, with unexpect benefit in increasing hippocampal gray matter volume. Despite a myriad of consequences following CIMT have been well documented, including enhanced neuronal sprouting and synapse formation, improved cortical representation of motor output and reduced excitability of contralateral cortex, changes in neuroplasticity at the network level and the restoration of function of remote brain regions are not well understood. With multidisciplinary approaches, the main goal of this proposal will determine whether CIMT restores neocortical-hippocampal network, enhances hippocampal neurogenesis and function. PUBLIC HEALTH RELEVANCE: Stroke affects the function of brain regions far away from the area that directly suffers from the ischemic attack. This intriguing neurological phenomenon has been described in 1914 among the scientific community and remains poorly understood. We have developed and characterized an animal model of stroke to study the mechanism of this type of brain dysfunction. To extend our previous findings, we will determine whether motor enrichment attenuates ischemia-induced disruption of neocortical-hippocampal network activity and promotes endogenous regeneration.